Biomedical subjects
Publications and source records attributed to J Ferin.
A technique that is based on the combined use of a conventional transmission electron microscope and a conventional electron probe x-ray microanalyzer permits an unambiguous identification of titanium dioxide (TiO2) particles in lung tissue and cells. Quite probably, many other inorganic particles can be identified with the use of this technique.
This study evaluated the effect of a low concentration of hydrogen sulfide on the rat antibacterial defense system. Rats exposed to 45 ppm hydrogen sulfide (threshold limit value for hydrogen sulfide = 10 ppm) for 4 or 6 hr exhibited a significant (P less .01) reduction in the inactivation of viable staphylococci deposited in the lungs during a bacterial aerosol challenge. Pre-exposure of rats to 46 ppm hydrogen sulfide for 2 hr, however, did not alter intrapulmonary staphylococcal inactivation. We hypothesize that impairment of the alveolar macrophage is the basis of these findings.
Using intratracheal instillation of radioactively labeled plastic microspheres of 3.3 and 10.3 microns diameter at two dose levels, this 7-month study in male Fischer 344 rats was designed to test a volumetric particulate burden hypothesis that has been proposed as a mechanistic basis for the condition of dust overloading of the lungs with highly insoluble particles of very low toxicity and to explain the prolongation of pulmonary particle retention. The study utilized airway and deep lung lavage techniques, scanning electron and optical microscopy of lavaged cells and lungs of sacrificed animals, particle distribution in alveolar macrophages (AM), fecal recovery of radioactive particles, and lung retention measurements by external counting. Microscopic assessments revealed that essentially all of the 3.3- and 10.3-microns-diameter particles were phagocytized by AM within 24 h postinstillation. One phagocytized 10.3-microns particle is capable of producing the hypothesized 600-microns 3/AM overload criterion for virtual AM immobilization. Neither the number nor the volume of 3.3-microns-diameter particles instilled was large enough to produce volumetric overloading assuming uniform distribution of the particles in the lung. In contrast to the 3.3-microns particles, the 10.3-microns particles were apparently sequestered to a greater extent and capable of greatly prolonging AM-mediated clearance of particles from the pulmonary region. The measured pulmonary retention half-times for the small and large particles were 86-109 days and 870-1020 days, respectively. Fecal recovery data closely complemented pulmonary clearance data for both particle sizes. The two-particle approach was found supportive of the volumetric overload hypothesis.
Recent epidemiological studies show an association between particulate air pollution and acute mortality and morbidity down to ambient particle concentrations below 100 micrograms/m3. Whether this association also implies a causality between acute health effects and particle exposure at these low levels is unclear at this time; no mechanism is known that would explain such dramatic effects of low ambient particle concentrations. Based on results of our past and most recent inhalation studies with ultrafine particles in rats, we propose that such particles, that is, particles below approximately 50 nm in diameter, may contribute to the observed increased mortality and morbidity In the past we demonstrated 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 range, approximately 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 milligrams per cubic meter range. In contrast, in the course of our most recent studies with thermodegradation products of polytetrafluoroethylene (PTFE) we found that freshly generated PTFE fumes containing singlet ultrafine particles (median diameter 26 nm) were highly toxic to rats at inhaled concentrations of 0.7-1.0 x 10(6) particles/cm3, 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 running 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 these fumes such as HF, carbonylfluoride, or perfluoroisobutylene, or to reactive radicals. The calculated mass concentration of the inhaled ultrafine PTFE particles in our studies was less than 60 micrograms/m3, a very low value to cause mortality in healthy rats. Aging of the fumes with concomitant aggregation of the ultrafine particles significantly decreases their toxicity. Since ultrafine particles are always present in the urban atmosphere, we suggest that they play a role in causing acute lung injury in sensitive parts of the population.
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