Lung deposition sites

The studies described above are important proof-of-principle investigations pointing to a debate about the carcinogenic hazard of MWNTs in the abdominal cavity. There are a number of open questions that need to be resolved before a final assessment can be made. In this respect, Oberdoster recently summarized such a challenge with three key questions do they (MWNTs) translocate from the deposition site in the lung to the pleura If so, what is the efficiency of such translocation in terms of the dose retained in pleural tissues What are the dimensions (in particular length) of the translocated MWNTs [92]. 

Figure 27.15. The deposition site of particles in the lung depends on particle size. Shown are predicted deposition patterns of (a) 5-pm particles, (b) 1-pm particles, and (c) 0.1-pm particles. (Adapted from Bennett, W. D., and Brown, J. S. Particulate dosimetry in the respiratory tract. In Foster, W. M., and Costa, D. L. (Eds.). Air Pollutants and the Respiratory Tract, 2nd edition. Taylor Francis, New York, 2005, pp. 21-73. This figure was completely redrawn by the author from materials cited.)...

The hazard from inhaled uranium aerosols, or any noxious agent, is determined by the likelihood that the agent will reach the site of its toxic action. Two main factors that influence the degree of hazard from toxic airborne particles are the site of deposition in the respiratory tract of the particles and the fate of the particles within the lungs. The deposition site within the lungs depends mainly on the particle size of the inhaled aerosol, while the subsequent fate of the particle depends mainly on the physical and chemical properties of the inhaled particles and the physiological status of the lungs. 

The use of a DPI may result in less total drug deposited in the lungs compared to an MDI, but alveolar deposition may be enhanced. It is not known if this difference in deposition site leads to any clinical benefit. 

The overall delivery of inhaled drugs to the effector site can be described by a number of steps. The variability in lung deposition thus depends on a large number of in vitro and in vivo factors—e.g., device performance, handling of the device, coordination of actuation and inhalation, inhalation flow, patient anatomy, etc. Variability in the different steps will add up to an overall variability in the amount of drug reaching the lungs. 

In the case of uptake via inhalation and/or wounds, and depending upon the initial chemical form the element(s), the lungs and/or wound site may be designated as a primary deposition site from which the actinide(s) will be transported to a secondary deposition site. 

Absorption into the blood depends on the physicoehemical form of the radionuclide deposited in the respiratoiy system, but is taken to be independent of deposition site, with the exception of ETj, from which no absorption is assumed. The model allows for changes in dissolution and absorption into blood with time. The use of material specific dissolution rates is recommended, but default absorption parameters are given for use when no specific information is available, namely types F (fast), M (moderate) and S (slow). These correspond broadly to the Pubhcation 30 default lung classes D (days), W (weeks) and Y (years) respectively, although the lung classes referred to overall clearance rates from the lung. 

In addition to size, the solubihty of particles is also important with regards to their deposition site. Typically, water-soluble particles are readily absorbed in all parts of the respiratory tract, whereas insoluble particles will remain inside the lung, due to their long retention time [85]. 

It appears that storage of absorbed beryllium takes place in the bones rather than in the soft tissues, though there is some transient retention in the liver, kidneys, and lungs. The sites of deposition appear to depend chiefly of the site of exposure and the nature of the beryllium compound, whether soluble or insoluble. It has been found that intramuscular infection of beryllium results in deposition of unexcreted portions of the bone. 

Figure 5 Sites of particle deposition assessed by confocal microscopy. Deposition sites of red and green fluorescent particles with a diameter of 2 am are shown in a bifurcation of a canine bronchiole surrounded by lung parenchyma. Please note, particles are marked with a thin white circle to improve their appearance in this black and white copy.

Valberg PA, Brain JD, Sneddon SL, LeMott SR. Breathing pattern influences aerosol deposition sites in excised dog lungs. J Appl Physiol 1982 53 824-837. 

Langenback EG, Bergofsky EH, Halpern JG, Foster WM. Determining deposition sites of inhaled lung particles and their effect on clearance. J Appl Physiol 1990 68 1427-1434. 

Toxicity. The toxicity of barium compounds depends on solubility (47—49). The free ion is readily absorbed from the lung and gastrointestinal tract. The mammalian intestinal mucosa is highly permeable to Ba " ions and is involved in the rapid flow of soluble barium salts into the blood. Barium is also deposited in the muscles where it remains for the first 30 h and then is slowly removed from the site (50). Very Httle is retained by the fiver, kidneys, or spleen and practically none by the brain, heart, and hair. 

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