Engineered Nanomaterials: Knowledge Gaps in Fate, Exposure, Toxicity, and Future Directions

Table 3

Inhalation toxicity of TiO₂ to rats and in vitro data on rat cell lines.

Reference	Exposed animals/cell line	Experimental design	Endpoint
Henrich et al. [113]	Wistar rats; inhalation	Chronic inhalation (24 months); 10 mg/m^3 TiO2 particles (15–40 nm size; mass-median aerodynamic diameter = 800 nm)	Carcinogenicity; histology; DNA addicts; alveolar lung clearance
Bermudez et al. [106]	Hamster and rat; inhalation	Subchronic inhalation (3.25 months); 10–250 mg/m^3 pigmentary TiO2 particles (assumed diameter = 300 nm; mass-median aerodynamic diameter = 1400 nm)	Inflammatory response; cytotoxicity; lung cell proliferation; histopathology
Höhr et al. [108]	Rat; instillation	16 h instillation; 1–6 mg (diameter = 20–30 nm and 180 nm)	Acute inflammatory response; cell damage
Bermudez et al. [107]	Hamster and rat; inhalation	Subchronic inhalation (13 weeks); 0.5–10 mg/m^3; diameter = 21 nm; mass-median aerodynamic; diameter = 1370 nm)	Inflammatory response; cytotoxicity; lung cell proliferation; histopathology
Renwick et al. [114]	Rat; instillation	24 h instillation; 0.125–0.5 mg; (diameter = 29 nm and 250 nm)	Inflammatory response; epithelial injury; alveolar macrophage toxicity; lung clearance
Warheit et al. [115]	Rat; instillation	24 h, 1-week, 1-month, and 3-month instillation; 129.4 nm; 149.4 nm; 136 nm; 382 nm	Bronchoalveolar lavage (BAL) fluid inflammatory markers; cell proliferation; histopathology
Grassian et al. [116]	Rat; inhalation	4 h duration and 10-day duration; 3.5 nm	Total protein content; LDH activity; inflammatory cytokines; histopathology
Li et al. [117]	Rat; inhalation	Three-day inhalation; 3 nm; 20 nm	BAL fluid biochemical parameters; histopathology
Lui et al. [118]	Rat; instillation	One-week instillation; 5–50 nm	Histopathology; blood biochemical parameters; LDH, alkaline phosphatase, and acid phosphatase activity; alveolar macrophage phagocytotic ability
Falck et al. [56]	Bronchial cells; (BEAS 2B)	Exposure to 8 doses (1–100 𝜇g/cm^2) of TiO2 particles: (1) nanorutile, (2) anatase with size <25 nm, and (3) fine rutile with size <5 μm for 24, 28, and 72 hours of exposure	DNA damage
Bhattacharya et al. [20]	Bronchial cells; (human BEAS 2B)	Toxicity of TiO2 particles in anatase crystal phase (size: <100 nm)	Reactive oxygen species (ROS) production; DNA adduct formation
Bhattacharya et al. [20]	Lung fibroblast cells; (IMR-90)	Toxicity of TiO2 particles in anatase crystal phase (size: <100 nm)	Cytotoxicity