A role for nanoparticle surface reactivity in facilitating pulmonary toxicity and development of a base set of hazard assays as a component of nanoparticle risk management

Abstract

Results of some lung toxicology studies in rats indicate that pulmonary exposures to ultrafine or nanoparticles produce enhanced inflammatory responses compared to fine-sized particles. Apart from particle size and corresponding surface area considerations, several additional factors may influence the lung toxicity of nanoparticles. These include surface reactivity or surface treatments/coatings of particles, and aggregation potential of aerosolized particles. Conclusions from three pulmonary bioassay hazard/safety studies are summarized herein and demonstrate that particle surface characteristics such as chemical reactivity often correlate better with pulmonary toxicity than particle size or surface area considerations. In the first study, fine-sized quartz particle exposures in rats (500 nm) produced similar effects (inflammation, cytotoxicity, cell proliferation, and/or histopathology) compared to smaller 12-nm nanoscale quartz particles. In another study, no measurable differences in lung toxicity indices were quantified when comparing exposure effects in rats to (1) fine-sized TiO₂ particles (300 nm, 6 m²/g [surface area]); (2) TiO₂ nanodots (6–10 nm, 169 m²/g); or (3) TiO₂ nanorods (27 m²/g). In a third study, exposures to ultrafine TiO₂ particles of similar sizes and different surface areas produced differential degrees of toxicity—based in large part upon surface reactivity endpoints—rather than particle size or surface area indices.

Finally, in a related issue for nanotechnology implications, a concept for developing a risk assessment system for the development of new nanomaterials is presented. Embodied in a Nanorisk framework process, implementation of a base set of toxicity tests for evaluating the health and environmental hazards related to nanoparticle exposures is discussed.

Keywords::

• α-quartz particles
• erythrocyte hemolysis
• nanoscale quartz particles
• particle characterization
• particle size
• pulmonary toxicity
• surface reactivity
• titanium dioxide particles
• ultrafine titanium dioxide particles
• vitamin C assay

Declaration of interest: This study was supported by the DuPont Company. Some of the TiO₂ particle-types discussed in this paper are made by the DuPont Company and are identified in the referenced studies (i.e. Warheit et al., 2006, 2007b and 2007c). The authors alone are responsible for the content and writing of the paper.