Acute Pulmonary Effects of Ultrafine Particles in Rats and Mice
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 575 Elmwood Avenue, Box EHSC, Rochester NY 14642, USA. Research report (Health Effects Institute)
08/2000; 96(96):5-74; disc. 75-86.
Ambient fine particles consist of ultrafine particles (< 100 nm) and accumulation-mode particles (approximately 100 to 1,000 nm). Our hypothesis that ultrafine particles can have adverse effects in humans is based on results of our earlier studies with particles of both sizes and on the finding that urban ultrafine particles can reach mass concentrations of 40 to 50 micrograms/m3, equivalent to number concentrations of 3 to 4 x 10(5) particles/cm3. The objectives of the exploratory studies reported here were to (1) evaluate pulmonary effects induced in rats and mice by ultrafine particles of known high toxicity (although not occurring in the ambient atmosphere) in order to obtain information on principles of ultrafine particle toxicology; (2) characterize the generation and coagulation behavior of ultrafine particles that are relevant for urban air; (3) study the influence of animals' age and disease status; and (4) evaluate copollutants as modifying factors. We used ultrafine Teflon (polytetrafluoroethylene [PTFE]*) fumes (count median diameter [CMD] approximately 18 nm) generated by heating Teflon in a tube furnace to 486 degrees C to evaluate principles of ultrafine particle toxicity that might be helpful in understanding potential effects of ambient ultrafine particles. Teflon fumes at ultrafine particle concentrations of approximately 50 micrograms/m3 are extremely toxic to rats when inhaled for only 15 minutes. We found that neither the ultrafine Teflon particles alone when generated in argon nor the Teflon fume gas-phase constituents when generated in air were toxic after 25 minutes of exposure. Only the combination of both phases when generated in air caused high toxicity, suggesting the existence of either radicals on the particle surface or a carrier mechanism of the ultrafine particles for adsorbed gas-phase compounds. We also found rapid translocation of the ultrafine Teflon particles across the epithelium after their deposition, which appears to be an important difference from the behavior of larger particles. Furthermore, the pulmonary toxicity of the ultrafine Teflon fumes could be prevented by adapting the animals with short 5-minute exposures on 3 days prior to a 15-minute exposure. This shows the importance of preexposure history in susceptibility to acute effects of ultrafine particles. Aging of the fresh Teflon fumes for 3.5 minutes led to a predicted coagulation resulting in particles greater than 100 nm that no longer caused toxicity in exposed animals. This result is consistent with greater toxicity of ultrafine particles compared with accumulation-mode particles. When establishing dose-response relationships for intratracheally instilled titanium dioxide (TiO2) particles of the size of the urban ultrafine particles (20 nm) and of the urban accumulation-mode particles (250 nm), we observed significantly greater pulmonary inflammatory response to ultrafine TiO2 in rats and mice. The greater toxicity of the ultrafine TiO2 particles correlated well with their greater surface area per mass. Ultrafine particles of carbon, platinum, iron, iron oxide, vanadium, and vanadium oxide were generated by electric spark discharge and characterized to obtain particles of environmental relevance for study. The CMD of the ultrafine carbon particles was approximately 26 nm, and that of the metal particles was 15 to 20 nm, with geometric standard deviations (GSDs) of 1.4 to 1.7. For ultrafine carbon particles, approximately 100 micrograms/m3 is equivalent to 12 x 10(6) particles/cm3. Homogeneous coagulation of these ultrafine particles in an animal exposure chamber occurred rapidly at 1 x 10(7) particles/cm3, so that particles quickly grew to sizes greater than 100 nm. Thus, controlled aging of ultrafine carbon particles allowed the generation of accumulation-mode carbon particles (due to coagulation growth) for use in comparative toxicity studies. We also developed a technique to generate ultrafine particles consisting of the stable isotope 13C by using 13C-graphite electrodes made in our laboratory from amorphous 13C powder. These particles are particularly useful tools for determining deposition efficiencies of ultrafine carbon particles in the respiratory tracts of laboratory animals and the translocation of particles to extrapulmonary sites. For compromised animals, we used acute and chronic pulmonary emphysema; a low-dose endotoxin inhalation aimed at priming target cells in the lung was also developed. Other modifying factors were age and copollutant (ozone) exposure. Exposure concentrations of the generated ultrafine particles for acute rodent inhalation studies were selected on the basis of lung doses predicted to occur in people inhaling approximately 50 micrograms/m3 urban ultrafine particles. Concentrations that achieved the same predicted lung burden per unit alveolar surface were used in rodents. (ABSTRACT TRUNCATED)
Available from: Constantini Samara
- "The potency of UFPs in terms of their proinflammatory and proallergic effects resides in their unique physical and chemical properties , including their small size that allows them to penetrate deep into the lung, where they are retained with a high rate of efficiency, large surface area, and coating with abundant redox-active OC compounds such as PAH and quinones (Li et al., 2010). Nevertheless, inhalation of model UFPs (carbon, platinum, Teflon) was not found to induce an inflammatory response in mice and rats (Oberdörster et al., 2000). On the other hand,Tong et al. (2010)observed significantly greater pulmonary inflammation in mice instilled with coarse PM than with fine or ultrafine PM, although ultrafine PM produced greater cardiovascular effects. "
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ABSTRACT: Current levels of ambient air particulate matter (PM) are associated with mortality and morbidity in urban populations worldwide. Nevertheless, current knowledge does not allow precise quantification or definitive ranking of the health effects of individual PM components and indeed, associations may be the result of multiple components acting on different physiological mechanisms. In this paper, healthy Balb/c mice were exposed to ambient PM10 at a traffic site of a large city (Thessaloniki, northern Greece), in parallel to control mice that were exposed to filtered air. Structural damages were examined in ultrafine sections of lung tissues by Transmission Electronic Microscopy (TEM). Ambient PM10 samples were also collected during the exposure experiment and characterized with respect to chemical composition and oxidative potential. Severe ultrastructural alterations in the lung tissue after a 10-week exposure of mice at PM10 levels often exceeding the daily limit of Directive 2008/50/EC were revealed mainly implying PM-induced oxidative stress. The DTT-based redox activity of PM10 was found within the range of values reported for traffic sites being correlated with traffic-related constituents. Although linkage of the observed lung damage with specific chemical components or sources need further elucidation, the magnitude of biological responses highlight the necessity for national and local strategies for mitigation of particle emissions from combustion sources.
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- "Many studies report the induction of pulmonary inflammation after exposure to nanomaterials, largely indicated by an influx of neutrophils that can be observed in the bronchoalveolar lavage fluid in vivo and the induction of inflammatory cytokines in in vitro lung models (eg. Ji et al., 2007; Pauluhn, 2011; Sung et al., 2009; Yang et al., 2008; Oberdorster et al., 2000; Warheit et al., 2007a, 2007b; Pauluhn, 2009). "
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ABSTRACT: The rapidly expanding manufacturing, production and use of nanomaterials has raised concerns for both worker and consumer safety. Various studies have been published in which induction of pulmonary inflammation after inhalation exposure to nanomaterials has been described. Nanomaterials can vary in aspects such as size, shape, charge, crystallinity, chemical composition, and dissolution rate. Currently, efforts are made to increase the knowledge on the characteristics of nanomaterials that can be used to categorise them into hazard groups according to these characteristics. Grouping helps to gather information on nanomaterials in an efficient way with the aim to aid risk assessment. Here, we discuss different ways of grouping nanomaterials for their risk assessment after inhalation. Since the relation between single intrinsic particle characteristics and the severity of pulmonary inflammation is unknown, grouping of nanomaterials by their intrinsic characteristics alone is not sufficient to predict their risk after inhalation. The biokinetics of nanomaterials should be taken into account as that affects the dose present at a target site over time. The parameters determining the kinetic behaviour are not the same as the hazard-determining parameters. Furthermore, characteristics of nanomaterials change in the life-cycle, resulting in human exposure to different forms and doses of these nanomaterials. As information on the biokinetics and in situ characteristics of nanomaterials is essential but often lacking, efforts should be made to include these in testing strategies. Grouping nanomaterials will probably be of the most value to risk assessors when information on intrinsic characteristics, life-cycle, biokinetics and effects are all combined.
Available from: Daifa Wang
- "The particles emitted by engines have a high proportion of nanoparticles, though most of them are in accumulation mode . Epidemiological studies have confirmed that air pollution makes adverse health effect, especially the pollutant in nanoscale  . Thus, nowadays most attention paid to airborne pollutants lies in nanoparticles and ultrafine particles. "
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ABSTRACT: The inhaled nanoparticles have attracted more and more attention, since they are more easily to enter the deep part of respiratory system. Some nanoparticles were reported to cause pulmonary inflammation. The toxicity of nanoparticles depends not only on its chemical component but also on the quantity and position of the deposition. The deposition of nanoparticles is not uniform and is influenced by airflow transport. The high deposition mainly occurs at the carinal ridges and the inside walls around the carinal ridges. Many factors could affect the transport and deposition of nanoparticles, such as particle size, flow rate, structure of airway, pulmonary function, and age. In this review, we discussed the methods and technique involved in particle transport and deposition studies. The features of particles deposition could be observed in clinic experiments and animal experiments. The mechanism of transport could be studied by numerical simulation. Numerical model and experiment study supplement each other. Some techniques such as medical imaging may support the study of nanoparticles transport and deposition. The knowledge of particles transport and deposition may be helpful both to defend the toxicity of inhaled particles and to direct inhaled drug delivery.
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