title: Differential mouse pulmonary dose and time course responses to titanium dioxide nanospheres and nanobelts.
abstract: Three anatase titanium dioxide (TiO(2)) nanoparticles (NPs) were prepared; nanospheres (NSs), short nanobelts (NB1), and long nanobelts (NB2). These NPs were used to investigate the effect of NP shape and length on lung toxicity. Mice were exposed (0-30 µg per mouse) by pharyngeal aspiration and pulmonary toxicity was assessed over a 112-day time course. Whole lung lavage data indicated that NB1- and NB2-exposed mice, but not NS-exposed mice, had significant dose- and time-dependent pulmonary inflammation and damage. Histopathological analyses at 112 days postexposure determined no interstitial fibrosis in any NS-exposed mice, an increased incidence in 30 µg NB1-exposed mice, and significant interstitial fibrosis in 30 µg NB2-exposed mice. At 112 days postexposure, lung burden of NS was decreased by 96.4% and NB2 by 80.5% from initial deposition levels. At 112 days postexposure, enhanced dark field microscopy determined that alveolar macro- phages were the dominant deposition site, but a fraction of NB1 and NB2 was observed in the alveolar interstitial spaces. For the 30 µg exposure groups at 112 days postexposure, confocal micro- scopy and immunofluorescent staining demonstrated that retained NB2 but not NS were present in the interstitium subjacent to the terminal bronchiole near the normal location of the smallest lymphatic capillaries in the lung. These lymphatic capillaries play a critical role in particle clearance, and the accumulation of NB2, but not NS, suggests possible impaired lymphatic clearance by the high aspect ratio particles. In summary, our data indicate that TiO(2) NP shape alters pulmonary responses, with severity of responses being ranked as NS < NB1 < NB2.
authors.affiliation: National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. dporter@cdc.gov
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Nianqiang
authors.initials: N
authors.lastname: Wu
authors.forename: Ann F
authors.initials: AF
authors.lastname: Hubbs
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Funk
authors.forename: Fanke
authors.initials: F
authors.lastname: Meng
authors.forename: Jiangtian
authors.initials: J
authors.lastname: Li
authors.forename: Michael G
authors.initials: MG
authors.lastname: Wolfarth
authors.forename: Lori
authors.initials: L
authors.lastname: Battelli
authors.forename: Sherri
authors.initials: S
authors.lastname: Friend
authors.forename: Michael
authors.initials: M
authors.lastname: Andrew
authors.forename: Raymond
authors.initials: R
authors.lastname: Hamilton
authors.forename: Krishnan
authors.initials: K
authors.lastname: Sriram
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Andrij
authors.initials: A
authors.lastname: Holian
mesh_terms: D000818:Animals; D001822:Body Burden; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D054118:Nanospheres / Q000737:chemistry / Q000633:toxicity / Q000648:ultrastructure; D010316:Particle Size; D011015:Pneumonia, Aspiration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014025:Titanium / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D004785:Environmental Pollutants; C009495:titanium dioxide; D014025:Titanium