title: Biokinetics and effects of barium sulfate nanoparticles.
abstract: 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 (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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Health, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. nkonduru@hsph.harvard.edu.
authors.forename: Nagarjun
authors.initials: N
authors.lastname: Konduru
authors.affiliation: Experimental Toxicology and Ecology, BASF SE, GV/TB - Z470, Carl-Bosch-Straße 38, Ludwigshafen, 67056, Germany. jana.keller@basf.com.
authors.forename: Jana
authors.initials: J
authors.lastname: Keller
authors.affiliation: Experimental Toxicology and Ecology, BASF SE, GV/TB - Z470, Carl-Bosch-Straße 38, Ludwigshafen, 67056, Germany. lan.ma-hock@basf.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma-Hock
authors.affiliation: Experimental Toxicology and Ecology, BASF SE, GV/TB - Z470, Carl-Bosch-Straße 38, Ludwigshafen, 67056, Germany. sibylle.groters@basf.com.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Gröters
authors.affiliation: Experimental Toxicology and Ecology, BASF SE, GV/TB - Z470, Carl-Bosch-Straße 38, Ludwigshafen, 67056, Germany. robert.landsiedel@basf.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.affiliation: Department of Environmental Health, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. donaghey@hsph.harvard.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Donaghey
authors.affiliation: Department of Environmental Health, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. brain@hsph.harvard.edu.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Brain
authors.affiliation: Experimental Toxicology and Ecology, BASF SE, GV/TB - Z470, Carl-Bosch-Straße 38, Ludwigshafen, 67056, Germany. wendel.wohlleben@basf.com.
authors.forename: Wendel
authors.initials: W
authors.lastname: Wohlleben
authors.affiliation: Department of Environmental Health, Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA. rmolina@hsph.harvard.edu.
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Molina
mesh_terms: D000284:Administration, Oral; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001465:Barium Radioisotopes; D001466:Barium Sulfate / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D019570:Inhalation Exposure / Q000009:adverse effects*; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D066237:Intestinal Elimination; D008168:Lung / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011921:Rats, Inbred WKY; D020545:Respiratory Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D065589:Respiratory Tract Absorption; D012995:Solubility; D014018:Tissue Distribution; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic; D066007:Toxicokinetics
chemical_list: D000393:Air Pollutants; D001465:Barium Radioisotopes; D001466:Barium Sulfate