Table 1.

Possible group-specific categories and modes of action for nanoparticles related to hazard and risk assessment

Group-specific considerations	Higher solubility particles	Poorly soluble, low toxicity (PSLT) particles	Poorly soluble, high toxicity particles	Fibrous particles
Example benchmark particles	Zinc oxide Copper oxide (I)	Titanium dioxide Carbon black	Crystalline silica Nickel oxide (III)	Carbon nanotubes Carbon nanofibers
Adverse effects	Acute lung effects Systemic toxicity	Lung inflammation and fibrosis; lung cancer (rats)	Chromiun oxide (III) Lung inflammation and fibrosis; lung cancer	Lung fibrosis, possible cancer, and mesothelioma
Mode of action	Toxic ions reach systemic tissues	Toxicity related to total deposited or retained particle dose in target respiratory tract region based on particle size	Same as PSLT; plus reactive surface (e.g., reactive oxygen species)	Durability/biopersistence Migration into alveolar walls and from lung tissue to the pleural Interference with normal cell division Genotoxicity
Dose metric related to adverse effects	Dissolution rate; amount absorbed into blood	Surface area Volume Mass or number, by particle size fraction	Same dose metrics as PSLT; plus reactivity of particle surface	Number of fibers of certain dimensions Total surface area of fibers or nanotubes
Dose–response relationship	Slope and effect level may depend on dissolution	May be nonlinear at low doses	Steeper slope and lower effect level than PSLT	Linear dose–response for some endpoints