PTFE (polytetrafluoroethylene) fumes consisting of large numbers of ultrafi
ne (uf) particles and low concentrations of gas-phase compounds can cause s
evere acute lung injury. Our studies were designed to test three hypotheses
: (i) uf PTFE fume particles are causally involved in the induction of acut
e lung injury, (ii) uf PTFE elicit greater pulmonary effects than larger si
zed 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 similar to 16 nm) generated by heating PTFE in a tube
furnace to 486 degreesC to evaluate principles of ultrafine particle toxic
ity. Teflon fumes at ultrafine particle concentrations of 50 mug/m(3) were
extremely toxic to rats when inhaled for only 15 min. We found that when ge
nerated in argon, the ultrafine Teflon particles alone are not toxic at the
se exposure conditions; neither were Teflon fume gas-phase constituents whe
n generated in air. Only the combination of both phases when generated in a
ir 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 pa
rticles compared to accumulation mode particles, although changes in partic
le surface chemistry during the aging process may have contributed to the d
iminished toxicity. Furthermore, the pulmonary toxicity of the ultrafine Te
flon fumes could be prevented by adapting the animals with short 5-min expo
sures 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 preexposu
re history for the susceptibility to acute ultrafine particle effects, (C)
2000 Academic Press.