title: The surface area rather than the surface coating determines the acute inflammatory response after instillation of fine and ultrafine TiO2 in the rat.
abstract: Alterations in the hydrophobic status of particle surfaces have been suggested to modify the toxic properties of ultrafine TiO2. We investigated the acute inflammatory responses and cell damage after intratracheal instillation of surface modified (hydrophilic and hydrophobic) fine (180 nm) and ultrafine (20-30 nm) TiO2 particles 16 h at equivalent mass (1 or 6 mg) and surface doses (100, 500, 600 and 3000 cm2) in rats. Inflammatory response and most enzyme levels were significantly related to the administered surface dose. The hydrophobic surface of the TiO2 particles, achieved by methylation, induced a lower total cell number and influx of neutrophils (PMN) compared to rats instilled with the 1 mg of the untreated, fine or ultrafine TiO2 but the outcomes were not statistically significant. No differences were observed between fine/ultrafine and hydophilic/hydrophobic TiO2 at the high dose (6 mg) or surface dose over 600 cm2. The differences in BAL cellularity at the low dose were reflected in changes in the chemokine MIP-2, but no differences were seen in levels of macrophage cytokines. Considering the large influx of PMN little cell damage was seen when studying enzyme leakage in lavage fluid, although PMNs appeared to be activated as suggested by increased myeloperoxidase (MPO) activity in the lavage fluid. We conclude that the surface area rather than the hydrophobic surface determines the acute, pulmonary inflammation induced by both fine and ultrafine TiO2.
authors.affiliation: Department of Fibre and Particle Toxicology, Institut für Umweltmedizinische Forschung (IUF), Düsseldorf, Germany. doris.hoehr@uni-duesseldorf.de
authors.forename: Doris
authors.initials: D
authors.lastname: Höhr
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Steinfartz
authors.forename: Roel P F
authors.initials: RP
authors.lastname: Schins
authors.forename: Ad M
authors.initials: AM
authors.lastname: Knaapen
authors.forename: Gianmario
authors.initials: G
authors.lastname: Martra
authors.forename: Bice
authors.initials: B
authors.lastname: Fubini
authors.forename: Paul J A
authors.initials: PJ
authors.lastname: Borm
mesh_terms: D000818:Animals; D018925:Chemokines / Q000494:pharmacology; D004396:Coloring Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000209:etiology*; D008171:Lung Diseases / Q000209:etiology* / Q000503:physiopathology; D008745:Methylation; D015394:Molecular Structure; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014025:Titanium / Q000009:adverse effects*
chemical_list: D018925:Chemokines; D004396:Coloring Agents; C009495:titanium dioxide; D014025:Titanium