G. Oberdorster et al., ASSOCIATION OF PARTICULATE AIR-POLLUTION AND ACUTE MORTALITY - INVOLVEMENT OF ULTRAFINE PARTICLES, Inhalation toxicology, 7(1), 1995, pp. 111-124
Recent epidemiological studies show an association between particulate
air pollution and acute mortality and morbidity down to ambient parti
cle concentrations below 100 mu g/m(3). Whether this association also
implies a causality between acute health effects and particle exposure
al these low levels is unclear at this time; no mechanism is known th
at would explain such dramatic effects of low ambient particle concent
rations. Based on results of our past and most recent inhalation studi
es with ultrafine particles in rats, we propose that such particles, t
hat is, particles below similar to 50 nm in diameter, may contribute t
o the observed increased mortality and morbidity. In the past we demon
strated that inhalation of highly insoluble particles of low intrinsic
toxicity, such as TiO2, results in significantly increased pulmonary
inflammatory responses when their size is in the ultrafine particle ra
nge, similar to 20 nm in diameter. However, these effects were not of
an acute nature and occurred only after prolonged inhalation exposure
of the aggregated ultrafine particles at concentrations in the milligr
ams per cubic meter range. In contrast, in the course of our most rece
nt studies with thermodegradation products of polytetrafluoroethylene
(PTFE) we found that freshly generated PTFE fumes containing singlet u
ltrafine particles (median diameter 26 nm) were highly toxic to rats a
t inhaled concentrations of 0.7-1.0 x 10(6) particles/cm(3), resulting
in acute hemorrhagic pulmonary inflammation and death after 10-30 min
of exposure. We also found that work performance of the rats in a run
ning wheel was severely affected by PTFE fume exposure. These results
confirm reports from other laboratories of the highly toxic nature of
PTFE fumes, which cannot be attributed to gas-phase components of thes
e fumes such as HF, carbonylfluoride, or perfluoroisobutylene, or to r
eactive radicals. The calculated mass concentration of the inhaled ult
rafine PTFE particles in our studies was less than 60 mu g/m(3), a ver
y low value to cause mortality in healthy rats. Aging of the fumes wit
h concomitant aggregation of the ultrafine particles significantly dec
reases their toxicity. Since ultrafine particles are always present in
the urban atmosphere, we suggest that they play a role in causing acu
te lung injury in sensitive parts of the population.