Paper | Particle | Model | Endpoints | Findings |
---|---|---|---|---|
Ahn et al., [14] | TiO2 (0.29 μm) | Intratracheal Instillation (4-72 hour exposure) -rats | BALF cell infiltration Number of goblet cells Muc5ac expression (indicative of mucus secretion) IL-13 production Histology (for lung tissue morphology) | Increased neutrophils, eosinophils & goblet cells Increased Muc5ac expression Increased IL-13 |
Renwick et al., [6] | TiO2 (29 & 250 nm) | Intratracheal Instillation (24 hour exposure) -rats | Inflammation (BALF analysis) Epithelial cell damage Lung permeability (BALF protein) Cytotoxicity (BALF LDH) Macrophage phagocytic ability (determining the uptake of fluorescent polystyrene particles) Macrophage chemotaxis (ability to migrate towards C5a) | NPs induce a neutrophil infiltration NPs damage epithelial cells Increased Lung permeability Increased Cytotoxicity NPs impair macrophage phagocytosis NP treated macrophages increased chemotaxis |
Chen et al., [12] | TiO2 (18-21 & 180-250 nm) | Intratracheal Instillation (3 day to 2 week exposure) -mice | Morphological analysis (included investigation of enlarged alveoli, disrupted septa, thickened alveoli) Apoptosis in lung tissue (TUNEL assay) Immunohistochemical staining (antiPCNA) cDNA microarray analysis rtPCR & Western Blot (for placenta growth factor (P1GF)) | Morphology of lung injury was emphysema-like for NPs. Observed macrophage infiltration that were particle laden Increased apoptosis in lung tissue Gene expression (chemokines & complement) changes indicative of an inflammatory response P1GF (a cytokine inducer) expression anticipated to be central to the inflammatory response • No pathology observed for fine particles |
Warheit et al., [11] | TiO2 (in various crystal forms) | Intratracheal instillation (24 hours to 3 month exposure) -rats | Inflammation (BALF cells & cytokines) Lung permeability (BALF protein) Cytotoxicity (BALF LDH) Epithelial cell secretory activity (alkaline phosphatase) Lung histopathology | Neutrophil infiltration No cytotoxicity, protein, alkaline phosphatase and lung morphology changes Macrophage accumulation but normal • Crystallinity of sample impacts on pulmonary toxicity (greater toxicity for anatase containing particles) |
Bermudez et al., [8] | TiO2 (1.40 μm) | Inhalation (13 week exposure) -mice, rats, hamsters | Inflammation (BALF & Histology) Lung particle burden Cytotoxicity (LDH) & permeability (protein) | High concentrations of particles administered impaired their clearance from the lung. However, hamsters were able to most efficiently clear particles. Inflammatory response evident in all species, but was most severe and persistent in rats. Increased LDH & protein (least severe in hamsters) Species differences, and dose dependent effects observed |
Bermudez et al., [7] | TiO2 (21 nm) | Inhalation (13 week exposure) -mice, rats, hamsters | Inflammation (BALF & Histology) Lung particle burden Cytotoxicity (LDH) & permeability (protein) | Retained particle burden decreased with (post-exposure) time & particles contained in macrophages Increased cellular infiltration (macrophages and neutrophils) dependent on species Increased LDH & protein (not hamsters) • Findings dependent on species (rats>mice>hamsters) and particle concentration |
Heinrich et al., [13] | TiO2 (also diesel soot and ufCB treatment groups) | Inhalation (2 year exposure (with satalite groups at 3, 6, 12 & 18 months), with or without subsequent clean air exposure for 6 months post particle exposure) -rats and mice | Histology (to assess Carcinogenicity) DNA adducts Lung particle burden Alveolar lung clearance BALF cytology and biochemical (including LDH, protein) analysis | Increased mortality with TiO2 (although mortality was also high in the control group) Alveolar lung clearance compromised by TiO2 Increased protein, LDH in BALF Increased lung tumours |
Ferin et al., [3] | TiO2 (12, 21, 230 & 250 nm) | Intratracheal instillation (24 hour exposure) Inhalation (12 week exposure) -rats | Inflammation (BALF neutrophil infiltration & histology) Lung burden & particle clearance | Neutrophil infiltration (greater for smaller particles) Particles internalised by alveolar macrophages Particle clearance slower for smaller particles, and access the pulmonary interstitium to a larger extent than fine particles |
Grassian et al., [10] | TiO2 (5 & 21 nm) | Inhalation (4 hour exposure will observations made immediately or 24 hours post exposure) Nasal instillation (24 hour exposure) -mice | Inflammation (BALF cells & cytokines) Cytotoxicity (BALF LDH) Lung Permeability (BALF protein) Lung histopathology (inflammation, lung injury, and abnormalities in pulmonary architecture) | Inhalation: macrophage infiltration, no changes in protein, LDH & histopathology Nasal instillation: neutrophil infiltration, increased IL-1β, IL-6, protein and LDH for 21 nm NPs only • 21 nm NPs more toxic than 5 nm NPs (due to agglomeration differences) |
Warheit et al., [9] | 6 samples of TiO2 (of various surface coatings, size up to 440 nm) | Inhalation (4 week exposure, with observations made at 2 weeks to 1 year post exposure) Intratracheal instillation (24 hours to 3 month exposure) -rats | Inflammation (BALF) Lung permeability (BALF protein) Cytotoxicity (BALF LDH) Histopathology | Inhalation: particle containing macrophage accumulation, epithelial cell hyperplasia, fibrotic response (collagen deposition) Intratracheal: neutrophil infiltration, particle laden macrophages, increased lung permeability, ncreased cytotoxicity • Surface treatment paramount to toxicity: aluminia and silica coatings increase toxic potency • The pulmonary toxicity of the particle panel overall was low & was similar in inhalation and instillation set ups |