(209e) Comprehensive Toxicity Evaluation of Carbon Nanoparticles

The burgeoning use of engineered nanomaterials (ENM) presents a rapidly evolving public health challenge as very little is known about their health effects. To address gaps in our current understanding, detailed studies on exposure assessment, physicochemical determinants of ENM toxicity, methods to measure and predict systemic health risk/toxicity and risk assessment of ENM at the cell, tissue and animal levels are warranted. Carbon nanoparticles such as buckyball, carbon nano tubes/nanofibers (CNTs/CNFs) represent by far the most widely studied ENM in industry and academia. The scientific community is most concerned with the potential toxicity of their exposure because of their increasing use in manufacturing, putative potential for cardiopulmonary effects, lack of monitoring tools, and limited understanding of physicochemical determinants of toxicity.

We have carried out a comprehensive evaluation of the toxicology of carbon nanoparticles from the single cell level in vitro to an animal model in vivo by combining a novel nanotechnology with conventional cellular toxicity and inhalational exposure study. At the cellular level, we used a nanochannel-electroporation (NEP) method that is capable of delivering nanoparticles with different size, geometry and surface chemistry, into individual cells with precise dose control. The basic element of NEP consists of two microchannels connected by a nanochannel. The cell to be transfected is positioned in one microchannel against the nanochannel and the other microchannel is filled with the agent to be delivered. A voltage pulse(s) lasting milliseconds (ms) is delivered between the two microchannels causing transfection. We achieve dose control by adjusting the duration and number of pulses. NEP provides a unique opportunity for quantitative studies of cytotoxicity of nanoparticles such as CNTs/CNFs at the single cell level. Cell viability, cell cycle, inflammation, oxidative stress, apoptosis, and CNTs/CNFs localization within the cell are compared with conventional cellular toxicity study of CNTs/CNFs using a large number of cells.

In vivo, a whole body exposure system is applied to carry out the nanoparticle delivery to mice. The particles are dispersed in air by an acoustical particle generator. The airborne particles are carried by air and entered the head/nose only exposure chamber for inhalation by a group of mice. Part of the aerosol is sampled through a Scanning Mobility Particle Sizer (SMPS, TSI Inc.) and an Ultrafine Water Condensation Particle Counter (UWCPC, TSI Inc.) to determine the particle size distribution and concentration. Cardiopulmonary health effects of particles are investigated under acute and possibly chronic in vivo exposures.

The combination of NEP, conventional cellular toxicity study and inhalational exposure study enable better understanding of toxicology of carbon nanoparticles. The methods developed may be applicable to other types of nanoparticles or toxic materials and in other exposure settings.