title: Biopersistence and translocation to extrapulmonary organs of titanium dioxide nanoparticles after subacute inhalation exposure to aerosol in adult and elderly rats.
abstract: The increasing industrial use of nanoparticles (NPs) has raised concerns about their impact on human health. Since aging and exposure to environmental factors are linked to the risk for developing pathologies, we address the question of TiO2NPs toxicokinetics in the context of a realistic occupational exposure. We report the biodistribution of titanium in healthy young adults (12-13-week-old) and in elderly rats (19-month-old) exposed to 10mg/m3of a TiO2nanostructured aerosol 6h/day, 5days/week for 4 weeks. We measured Ti content in major organs using inductively coupled plasma mass spectrometry immediately and up to 180days after the end of exposure. Large amounts of titanium were initially found in lung which were slowly cleared during the post-exposure period. From day 28, a small increase of Ti was found in the spleen and liver of exposed young adult rats. Such an increase was however never found in their blood, kidneys or brain. In the elderly group, translocation to extra-pulmonary organs was significant at day 90. Ti recovered from the spleen and liver of exposed elderly rats was higher than in exposed young adults. These data suggest that TiO2NPs may translocate from the lung to extra-pulmonary organs where they could possibly promote systemic health effects.
authors.affiliation: Institut National de Recherche et de Sécurité, Département Toxicologie et Biométrologie, Rue du Morvan, CS 60027, F-54519 Vandœuvre Cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gaté
authors.affiliation: Service de Pharmacolog¡e et Immuno-Analyse (SPI), IBITECS, CEA, Université Paris-Saclay, F91191 Gif-sur-Yvette, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Disdier
authors.affiliation: Institut National de Recherche et de Sécurité, Département Toxicologie et Biométrologie, Rue du Morvan, CS 60027, F-54519 Vandœuvre Cedex, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cosnier
authors.affiliation: Institut National de Recherche et de Sécurité, Département Toxicologie et Biométrologie, Rue du Morvan, CS 60027, F-54519 Vandœuvre Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Gagnaire
authors.affiliation: Institut National de Recherche et de Sécurité, Département Toxicologie et Biométrologie, Rue du Morvan, CS 60027, F-54519 Vandœuvre Cedex, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Devoy
authors.affiliation: Inserm, CEA, Université Paris Sud, UMR 1023 - ERL 9218 CNRS, IMIV, F-91406 Orsay, France.
authors.forename: Wadad
authors.initials: W
authors.lastname: Saba
authors.affiliation: Laboratoire de Chimie Physique, UMR CNRS 8000, Université Paris Sud, F-91405 Orsay, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Brun
authors.affiliation: Institut National de Recherche et de Sécurité, Département Toxicologie et Biométrologie, Rue du Morvan, CS 60027, F-54519 Vandœuvre Cedex, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Chalansonnet
authors.affiliation: Service de Pharmacolog¡e et Immuno-Analyse (SPI), IBITECS, CEA, Université Paris-Saclay, F91191 Gif-sur-Yvette, France. Electronic address: aloise.mabondzo@cea.fr.
authors.forename: Aloise
authors.initials: A
authors.lastname: Mabondzo
mesh_terms: D000336:Aerosols; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001822:Body Burden; D019570:Inhalation Exposure / Q000009:adverse effects / Q000032:analysis*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009928:Organ Specificity; D010316:Particle Size; D011916:Rats, Inbred F344; D013499:Surface Properties; D013997:Time Factors; D014018:Tissue Distribution; D014025:Titanium / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D066007:Toxicokinetics
chemical_list: D000336:Aerosols; C009495:titanium dioxide; D014025:Titanium
keywords: Biodistribution; Inhalation exposure; Nanoparticles aerosol; Titanium dioxide