PTFE (polytetrafluoroethylene) fumes consisting of large numbers of ultrafine (uf) particles and low concentrations of gas-phase compounds can cause severe acute lung injury. Our studies were designed to test three hypotheses: (i) uf PTFE fume particles are causally involved in the induction of acute lung injury, (ii) uf PTFE elicit greater pulmonary effects than larger sized PTFE accumulation mode particles, and (iii) preexposure to the uf PTFE fume particles will induce tolerance. We used uf Teflon (PTFE) fumes (count median particle size approximately 16 nm) generated by heating PTFE in a tube furnace to 486 degrees C to evaluate principles of ultrafine particle toxicity. Teflon fumes at ultrafine particle concentrations of 50 microg/m(3) were extremely toxic to rats when inhaled for only 15 min. We found that when generated in argon, the ultrafine Teflon particles alone are not toxic at these exposure conditions; neither were Teflon fume gas-phase constituents when generated in air. Only the combination of both phases when generated in air caused high toxicity, suggesting either the existence of radicals on the surface or a carrier mechanism of the ultrafine particles for adsorbed gas compounds. Aging of the fresh Teflon fumes for 3.5 min led to a predicted coagulation to >100 nm particles which no longer caused toxicity in exposed animals. This result is consistent with a greater toxicity of ultrafine particles compared to accumulation mode particles, although changes in particle surface chemistry during the aging process may have contributed to the diminished toxicity. Furthermore, the pulmonary toxicity of the ultrafine Teflon fumes could be prevented by adapting the animals with short 5-min exposures on 3 days prior to a 15-min exposure. Messages encoding antioxidants and chemokines were increased substantially in nonadapted animals, yet were unaltered in adapted animals. This study shows the importance of preexposure history for the susceptibility to acute ultrafine particle effects.

Copyright 2000 Academic Press.