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Part Fibre Toxicol. 2008 Dec 1;5:17. doi: 10.1186/1743-8977-5-17.

Pulmonary response to intratracheal instillation of ultrafine versus fine titanium dioxide: role of particle surface area.

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Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.



The production and use of nanoparticles is growing rapidly due to the unique physical and chemical properties associated with their nano size and large surface area. Since nanoparticles have unique physicochemical properties, their bioactivity upon exposure to workers or consumers is of interest. In this study, the issue of what dose metric (mass dose versus surface area dose) is appropriate for toxicological studies has been addressed. Rats were exposed by intratracheal instillation to various doses of ultrafine or fine TiO2. At 1, 7, or 42 days post-exposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium) basis.


The findings of the study show that on a mass basis the ultrafine particles caused significantly more inflammation and were significantly more cytotoxic than the fine sized particles. However, when doses were equalized based on surface area of particles delivered, the ultrafine particles were only slightly more inflammogenic and cytotoxic when compared to the fine sized particles. Lung burden data indicate that ultrafine TiO2 appears to migrate to the interstitium to a much greater extent than fine TiO2.


This study suggests that surface area of particles may be a more appropriate dose metric for pulmonary toxicity studies than mass of particles.

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