Lung particle overload

Oberdorster G (1995) The NTP talc inhalation study A critical appraisal focused on lung particle overload. Regulatory Toxicology and Pharmacology 21 233-241. 

Oberdorster, G. (1995a). Lung particle overload Implications for occupational exposures to particles. Regul Toxicol Pharmacol 21(1), 123—135. 

ILSI (2000). The relevance of the rat lung response to particle overload for human risk assessment A workshop consensus report. Inhal Toxicol 12(1), 1-17. 

An outgrowth of debate over these and related findings was the concept of particle overload in the lung (33,34,65,69-72). Particle overload was a key topic of discussion at a symposium honoring Paul Morrow and subsequently published as a special issue of the Journal of Aerosol Medicine in 1990. In a discussion of the health effects of highly insoluble, low-toxicity particles in that issue, I defined lung overload as... 

McClellan RO. Particle overload in the lung approaches to improving our knowledge, J Aerosol Med 1990 3(suppl) S197-S207. 

Mauderly JL, McCunney RJ, eds. Particle Overload in the Rat Lung and Lung Cancer, Proceedings of a Conference Held at the Massachusetts Institute of Technology on March 29 and 30, 1995. Inhal Toxicol 1996 8(suppl) 1-288. 

Another way of approaching the problem is to put the lung into overload, which for convenience, can be defined as a situation in which administration of sufficiently high loads of nontoxic insoluble dusts produces marked prolongation or even total failure of macrophage-mediated particle clearance (reviewed in 41,91). The mechanism of the overload effect is not entirely understood (see 91-94 for comments), but it is clear that, under overload conditions, the burden of free particles in the alveoli, the number of particles that are taken up by epithelial cells, and the number of particles translocated to the interstitium, all are greatly increased (41,91). 

The potential consequences of inhalation exposure to nanoparticles are only beginning to be nnderstood. The toxicology of metal fumes, radionuclides, nuisance dusts, rat lung overload, the toxicology of sihca, asbestos, synthetic vitreous fibers, and pollution particles can aU be used to gain insight into the behavior of nanoparticles. Currently, there is no model to predict the toxicity or safety of nanoparticles, and little information is available with regard to human exposure and risks related to levels and duration of exposure. 

Oberdorster G, Ferin J, Soderholm SC, Gelein R, Cox C, Baggs R, Morrow PE. Increased pulmonary toxicity of inhaled ultrafine particles due to lung overload alone Ann Occup Hyg 1994 38(suppl l) 295-302. 

Muhle H, Bellmann B, Heinrich U. Overloading of lung clearance during chronic exposure of experimental animals to particles. Aim Occup Hyg (Inhaled Particles VI) 1988 32 141-147. 

All inhaled particles evoke an inflammatory response in the lung. In most reported studies the initial inflammatory cells are polymorphonuclear leukocytes (PMNL), and these are followed by an influx of alveolar macrophages (1,41,49,64-68,78,89). In a few studies (55,70) only a macrophage response has been seen, at least when considering cells accumulating at the first alveolar duct bifurcations, the major site of particle impaction in these specific experiments. As a rule, and provided the point of overload (see following) is not reached, there is a reasonably good correlation between the number of particles deposited and... 

Experiments in which the lung is put into overload (40,41) also illustrate the deleterious effects of epithelial particle uptake, because under overload conditions, a variety of particles that are normally considered to be nonpathogenic (carbon black, titanium dioxide, copier toner, volcanic fly ash, and diesel exhaust) produce interstitial inflammation and fibrosis. Many also produce lung cancers in rats, although the latter phenomenon is probably restricted to rats (37,41,91,92) and appears not to occur in other species. 

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