Toxicology of ultrafine particles:: in vivo studies

Ultrafine particles (less than 100 nm in diameter) are encountered in ambient air and at the workplace. Normal background levels in the urban atmosphere for ultrafine particles are in the range 1-4 x 10(4) cm(-3); however, their mass concentration is normally not greater than 2 mug m(-3). At the workplace, ultrafine particles occur regularly in metal fumes and polymer fumes, both of which can induce acute inflammatory responses in the lung upon inhalation. Although ultrafine particles occurring at the workplace are not representative, and, therefore, are not relevant for urban atmospheric particles, their use in toxicological studies can give valuable information on principles of the toxicity of ultrafine particles. Studies in rats using ultrafine polymer fumes of polytetrafluoroethylene (PTFE) (count median diameter ca. 18 nm) showed that (i) they induced very high pulmonary toxicity and lethality in rats after 15 min of inhalation at 50 mug m(-3); (ii) ageing of PTFE fumes resulted in agglomeration to larger particles and loss of toxicity; (iii) repeated pre-exposure for very short periods protected against the toxic and lethal effects of a subsequent 15 min exposure; (iv) rapid translocation of PTFE particles occurred to epithelial, interstitial and endothelial sites. Since one characteristic of urban ultrafine particles is their carbonaceous nature, exposure of rats to laboratory-generated ultrafine carbonaceous (elemental, and organic, carbon) particles was carried out at a concentration of ca. 100 mug m(-3) for 6 h. Modulating factors of responses were prior low-dose inhalation of endotoxin in order to mimic early respiratory tract infections, old age (22-month old rats versus 10-week old rats) and ozone co-exposure. Analysis of results showed that (i) ultrafine carbon particles can induce slight inflammatory responses (ii) LPS priming and ozone co-exposure increase the responses to ultrafine carbon; (iii) the aged lung is at increased risk for ultrafine particle-induced oxidative stress. Other studies with ultrafine and fine TiO2 showed that the same mass dose of ultrafine particles has a significantly greater inflammatory potential than fine particles. The increased surface area of ultrafine particles is apparently a most important determinant for their greater biological activity. Ln addition. the propensity of ultrafine particles to translocate may result in systemic distribution to extrapulmonary tissues.