title: Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties.
abstract: Surface properties are critical to assess effects of ultrafine-TiO(2) particles. The aim of this study was to assess lung toxicity in rats of newly developed, well characterized, ultrafine-TiO(2) particles and compare them to TiO(2) samples in two different size ranges and surface modifications. Groups of rats were intratracheally instilled with doses of 1 or 5mg/kg of either two ultrafine rutile TiO(2) particles (uf-1 or uf-2); rutile R-100 fine-TiO(2) (F-1); 80/20 anatase/rutile P25 ultrafine-TiO(2) (uf-3); or alpha-quartz particles. Phosphate-buffered saline (PBS) solution instilled rats served as vehicle controls. Following exposures, the lungs of PBS and particle-exposed rats were evaluated for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation, and by histopathology at post-instillation time points of 24h, 1 week, 1 and 3 months. The ranking of lung inflammation/cytotoxicity/cell proliferation and histopathological responses was quartz>uf-3>F-1=uf-1=uf-2. Exposures to quartz and to a lesser degree, uf-3 anatase/rutile TiO(2) particles produced pulmonary inflammation, cytotoxicity and adverse lung tissue effects. In contrast, exposures to F-1 fine-TiO(2) particles or to uf-1/uf-2 ultrafine-TiO(2) particle-types produced transient inflammation. We conclude that differences in responses to anatase/rutile uf-3 TiO(2) particles versus the rutile uf-1 and uf-2 TiO(2) particles could be related to crystal structure, inherent pH of the particles, or surface chemical reactivity. Thus, based on these results, inhaled rutile ultrafine-TiO(2) particles are expected to have a low risk potential for producing adverse pulmonary health effects. Finally, the results demonstrate that exposures to ultrafine-TiO(2) particle-types can produce differential pulmonary effects, based upon their composition, and crystal structure. Thus, the lung toxicity of anatase/rutile uf-3 should not be viewed as representative for all ultrafine-TiO(2) particle-types.
authors.affiliation: DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714-0050, USA. david.b.warheit@usa.dupont.com
authors.forename: David B
authors.initials: DB
authors.lastname: Warheit
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Webb
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Reed
authors.forename: Scott
authors.initials: S
authors.lastname: Frerichs
authors.forename: Christie M
authors.initials: CM
authors.lastname: Sayes
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D011791:Quartz / Q000633:toxicity; D051381:Rats; D013499:Surface Properties; D007507:Therapeutic Irrigation; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D011791:Quartz; C009495:titanium dioxide; D014025:Titanium; D007770:L-Lactate Dehydrogenase